We have studied single stranded (ss) RNA binding immunoglobulins in the sera of patients with systemic lupus erythematosus as part of a project to obtain antibodies with conformational specificity for nucleic acids. The antibody population that bound polyribonucleotides and the population that bound polydeoxyribonucleotides appear to be distinct. The anti ss-RNA antibodies preferentially bound native ssRNA (as compared with synthetic polyribonucleotides) with an increasing affinity for the higher molecular weight RNA's. We have also developed an assay for detection of specific RNA antibodies, produced in vitro by spleen cells from old female NZB/NZW F1 mice. This assay enables one to test the effect of different therapeutic agents at the immediate site of antibody synthesis. In related studies of nucleic acid purification, we have shown that gel bound ethidium bromide, a nucleic acid intercalating agent, can interact with transfer ribonucleic acid and this interaction can be used as a basis for column chromatographic fractionation.